When cells are exposed to stressful stimuli (e.g. heat shock, UV irradiation, hyper-osmotic conditions, inflammatory cytokines), they initiate responses that are associated with both survival and programmed cell death. The interactions between and relative activation of the signaling pathways that mediate these responses determines the ultimate fate of the stressed cell. Our understanding of the molecular decision-making processes that govern stress tolerance has important implications for human health in light of the fact that these processes are intimately linked to cellular aging, tumor cell resistance to therapeutic intervention, and normal as well as detrimental immune responses. Because the relevant signaling pathways are highly complex in humans and other mammals, simpler eukaryotes are valuable and accessible model systems for the elucidation of these fundamental survival strategies. We have been investigating mechanisms of stress tolerance in the model organism Dictyostelium discoideum, and have identified a novel gene that is induced by heat stress and that encodes a unique protein tyrosine phosphatase-like polypeptide. The specific objective of this research project is to test the hypothesis that (1) the polypeptide encoded by this heat-induced gene is a functional protein tyrosine or dual-specificity phosphatase; and (2) that this regulatory enzyme plays a role in signal transduction pathways that mediate cellular stress responses in Dictyostelium.